Low back pain is a widespread disorder that creates much patient suffering and exerts a tremendous economic burden on society. While this condition is multifactorial, intervertebral disc degeneration is one of its main causes. Degeneration starts in the compressible core of the intervertebral disc (i.e. the nucleus pulposus, NP). It is characterized by the inability of the resident cells to keep the NP tissue intact due to a change of their phenotype and their decreasing number. Actual treatments are only symptomatic (aimed at alleviating pain) and new therapies able to reverse the degenerative process are crucially needed. Thus, delivery of exogenous cells, such as mesenchymal stem cells (MSCs), has been proposed to help to NP repair. These cells, however, had only a limited success, with disc degeneration inhibited but not reversed. Because of its avascular nature, the intervertebral disc relies solely on diffusion for its nutrient supply. As a result, NP cells are physiologically exposed to hypoxia, nutrient deprivation and low pH. As degeneration progresses some of these environmental factors worsen. This challenging environment may explain the loss of function of NP cells as well as the sub-optimal results obtained with MSCs. In fact, some studies already begun to look at the effects of low oxygen and glucose levels on NP cells and MSCs and they showed that glucose, rather than oxygen, was critical for cell survival. Providing an adequate glucose supply to a degenerated disc can, therefore, help to promote tissue repair by resident NP cells as well as by exogenous MSCs. The SLiGRIv project proposes to improve native NP cell and exogenous MSC survival and functions in degenerative discs by its improving glucose supply with injectable glucose delivery systems. The first step of the project (WP1) will test two strategies to increase local concentration of glucose either by enzymatic degradation of a glucose polymer or by glucose diffusion from hydrogels with increased viscosity. Hydrogel compositions will be optimized for a sustain delivery of physiological doses of glucose. Hydrogels will also be tested for their injecting properties and for their effects on disc mechanical properties. In the second step of the project (WP2), the optimized hydrogels will be tested on human degenerated NP samples, using an explant culture system. Their effects on NP cell viability and phenotype and NP matrix turn-over will be evaluated. The third step of the project (WP3) will, then, evaluate the potential benefit of combining the optimized hydrogels with exogenous MSCs to promote NP repair using the same NP explant system and same analysis methods than in WP2. If adding MSCs improves NP repair, WP3 will also try to elucidate the mechanisms beyond this effect (i.e. via MSC differentiation or via MSC paracrine effects). Finally, the last step of the project (WP4) will provide the in vivo proof-of-concept that glucose delivery can promote NP repair, with or without the addition of exogenous MSCs, in an animal model of disc degeneration. The ability of the proposed therapy to restore disc height, hydration and mechanical properties will be assessed. The SLiGRIv project will provide an innovative strategy to overcome hurdles encountered by regenerative therapies for the intervertebral disc degeneration.

In the past years, surfactants produced from biomass have been intensively developed. However the high-quality fractions of biomass are in competition with food applications. Silk proteins appear as non-food natural polymers which utilization for surfactant production has been sparsely studied. The main objective of LIPOSILK project is to develop an original way for the biomass valorization to produce a new class of silk protein based surfactants. A multidisciplinary approach will be used integrating new eco-friendly synthesis, study of surfactant structural variations and its performances, and evaluation of the environmental impacts. The main novelty of this project is the use of new green methodologies in solvent less condition for surfactant production. The originality of this project consists in complete study for biosurfactant design, including the extraction of protein, chemical and enzymatic modifications to obtain lipopeptides, full characterization of adsorption, physico-chemical, biological properties and life cycle assessment analysis of obtained molecules. Lipopeptide molecules developed in LIPOSILK project could be possibly used as mild surfactants in cosmetics, toiletry and pharmaceutical products for topical treatment.

The impaired skeleton, characterized by an increased fracture risk and compromised bone healing, is a newly recognized and poorly described complication of type 2 diabetes mellitus (T2DM). DIABONE offers a unique perspective to address this issue through seven interdisciplinary work packages. By crossing the boundaries between the fields of bone biology, endocrinology, biomaterials, stem-cell based regenerative medicine and inflammation, DIABONE project will ultimately translate into changes in orthopaedic practice by providing mechanistic-based insights for treating bone fractures and defects of patients with T2DM and establishing the proof of concept for using a customized bone tissue engineered implant tailored to the diabetic host bed. Taking place in nine dynamic and experienced host laboratories composing the consortium,DIABONE aims to catalyse the significant development of early stage researchers by offering these the opportunity to reach a position of professional maturity, diversity and independence in order to enhance their contribution to the knowledge-based European economy and society

The dura mater is the most external meningeal tissue (above arachnoid and pia mater) and consists of a half-rigid membrane located between the central nervous system (brain, spinal cord) and the surrounding bone tissue (skull, vertebrae). The dura mater is made of several layers of collagen fibres with various diameters and orientations and provides essential biological, mechanical and protective functions, such as containing the cerebrospinal fluid (CSF) around the brain and the spinal cord. After neurosurgery implying dura mater filling or suture, the excessive or inappropriate scar of this tissue, known as epidural fibrosis, leads to CSF leakage, pain or even neurological symptoms in up to 20% of patients. Although such issues have been studied for several decades and dura mater substitutes have been developed, their use is no optimal and postoperative complications are still noticed. It is therefore mandatory to develop alternative, innovative solutions to improve patients’ health and well-being while saving costs related to longer and more frequent hospitalization periods (needs for a second surgery). In this context, this project aims at developing new biomimetic substitutes based on the multiphasic interface created by dura mater and skull bones as candidate substitutes to face these clinical challenges and offer easy handling to clinicians. Electrospinning will be used as the main production method thanks to the high structural similarity between the produced fibres and the dural extracellular matrix as well as the great versatility of this process. Well known in the field of biomaterial development, this technique is however barely investigated for the regeneration of meningeal tissues in despite of such similarities. Random fibres made of polycaprolactone, an FDA-approved polymer, will be turned into composite materials with modified properties (fibre diameter, porosity, alignment, mechanical properties). The objective is here to develop, thanks to an extensive in vitro cell characterization step, specific phases promoting respectively osteointegration, bioactivity of dural cells or dura mater wound healing. This project first aims at optimising the technical parameters allowing for the production of such scaffolds (WP1). After physico-chemical and cytotoxic characterization (WP2), the phases will be combined to create macroscopic structures and study their influence on auto-organization of cell co-cultures (stem cells, dural fibroblasts) and the impact of composition and structure of the biomaterials only on cell differentiation and functionality (WP3). Such an in vitro exhaustive cellular analysis will not only highlight the biomaterial properties leading to the best cell response but will also strengthen our knowledge of the in vitro behaviour of dural cells, still limited nowadays, as well as of the interactions between dura mater and skull bones. The most promising sets of parameters will then be validated through in vivo implantations in a rodent model of cranial defects to evaluate inflammatory reaction, biocompatibility and wound healing in comparison with an existing dural substitute (WP4). This in vivo proof-of-concept study will pave the way towards subsequent projects to refine, improve and complexify the candidate substitutes thanks to the versatility of the multiphasic approach (addition of layers with supplementary specific properties, extension to the other meningeal tissues) before further implantations assessing the influence on function recovery and long-term integration.

The project aims to develop and use fully three-dimensional computer simulations to investigate the correlation between the lymphatic vessel wall biochemically induced contraction and the opening-closing of valves, and its consequences on controlling the lymph fluid pumping. The project will consider fully fluid deformable structure interaction, and presence of multiple lymphangions and Y-junctions topology.